PROJECT SUMMARY/ABSTRACT Physical impairment is a highly prevalent and progressive problem that contributes to a significantly lower quality of life experienced by patients with end-stage renal disease (ESRD) undergoing thrice weekly hemodialysis. Observational data has shown that improper fluid management is a likely contributor to physical impairment, but lack of data on the relative importance of the many fluid-related components of dialysis therapy (e.g. intradialytic weight gain, baseline fluid overload, intradialytic blood pressure, ultrafiltration rate, and target weight achievement) has limited consensus and evidence-based guideline development. The Dialysis Rx to Yield Optimal UltrafilTration (DRYOUT) study is a proposed observational analysis of adult patients with ESRD receiving hemodialysis in San Francisco. The major goal of this study is to identify which elements of fluid overload, and its subsequent removal on dialysis, serve as the strongest predictors of physical performance. Identification of these risk factors may guide future clinical trials testing different fluid management strategies to improve how patients feel and function while on hemodialysis.